Methods for Mixing a Fluid with Foldable Impellers

ABSTRACT

A method of mixing a fluid includes at least partially unfolding a collapsible bag bounding a compartment, the collapsible bag containing in the compartment at least a portion of an elongated drive line or drive shaft and an impeller secured to the drive line or drive shaft, the impeller including a plurality of impeller blades that are pivotable relative to the drive line or drive shaft, at least one of the plurality of impeller blades being in a collapsed position. A fluid is delivered into the compartment of the collapsible bag. The drive line or drive shaft is then rotated so as to rotate the impeller within the compartment and mix the fluid therein, the at least one of the plurality of impeller blades pivoting from the collapsed position to an expanded position as the impeller is rotated within the compartment.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a divisional of U.S. application Ser. No.16/358,263, filed Mar. 19, 2019, which is a continuation of U.S.application Ser. No. 15/803,327, filed Nov. 3, 2017, now U.S. Pat. No.10,272,400, issued Apr. 30, 2019, which is a continuation of U.S.application Ser. No. 14/390,956, filed Oct. 6, 2014, now U.S. Pat. No.9,839,886, issued Dec. 12, 2017, which is a nationalization of PCTApplication No. PCT/US2013/031608, filed Mar. 14, 2013, which claims thebenefit of U.S. Provisional Application No. 61/621,064, filed on Apr. 6,2012, which are incorporated herein by specific reference.

BACKGROUND OF THE INVENTION 1. The Field of the Invention

The present invention relates to fluid mixing systems and, morespecifically, fluid mixing systems having a flexible drive line and/oran impeller having pivotable blades.

2. The Relevant Technology

The biopharmaceutical industry uses a broad range of mixing systems fora variety of processes such as in the preparation of media and buffersand in the growing, mixing and suspension of cells and microorganisms.Some conventional mixing systems, including bioreactors and fermentors,comprise a flexible bag disposed within a rigid support housing. Animpeller is disposed within the flexible bag and is coupled with thedrive shaft. Rotation of the drive shaft and impeller facilitates mixingand/or suspension of the fluid contained within the flexible bag.

Although the current mixing systems are useful, they have somelimitations. For example, where the drive shaft is secured within theflexible bag during the manufacturing process, the rigid drive shaftlimits the ability to collapse or fold the flexible bag so as to reduceits size for transportation, storage and/or further processing.Likewise, where it is intended to reuse the drive shaft, such as when itis made of metal, this system has the disadvantage of needing to cleanand sterilize the drive shaft between different uses.

In an alternative conventional system, a rotatable tube extends into theflexible bag and has an impeller coupled at the end thereof. During use,the rigid drive shaft is passed down into the tube and couples with theimpeller. In turn, rotation of the drive shaft facilitates rotation ofthe impeller for mixing the fluid within the flexible bag. In thisdesign, with the drive shaft removed, the flexible bag with tube can befolded for ease of storage and transportation. In addition, because thedrive shaft does not directly contact the fluid within the bag, thedrive shaft does not need to be cleaned or sterilized between uses.

However, the flexible bag is typically secured within the supporthousing prior to insertion of the drive shaft. It is thus necessaryduring use to vertically position the drive shaft over the top of thebag for insertion into the tube. For large bags or elongated bags thatrequire a long drive shaft, this can be difficult to accomplish.Furthermore, in situations where the mixing system is located in a roomwith a relatively low ceiling, it may be impossible to vertically liftthe drive shaft over the bag. This type of system also requiresincreased training in user operation to ensure that the drive shaft isproperly received within the tube and properly engaged with the impellerso that the system operates as intended.

Conventional systems also have the drawback that the rigid impellerslocated within the bags limit the extent to which the bags can becollapsed by folding or other manipulation. Likewise, there arepotential concerns that the blades of the impellers can puncture orotherwise damage the bags when the bags are folded around the impeller.In addition, folding the bag around the impeller can place unwantedstress on the rigid impeller blades.

Accordingly, what is needed in the art are mixing systems that solve allor some of the above problems.

BRIEF DESCRIPTION OF THE DRAWINGS

Various embodiments of the present invention will now be discussed withreference to the appended drawings. It is appreciated that thesedrawings depict only typical embodiments of the invention and aretherefore not to be considered limiting of its scope.

FIG. 1 is a perspective view of a support housing and docking stationforming part of a fluid mixing system;

FIG. 2 is a perspective view of a container assembly for use with asupport housing shown in FIG. 1 ;

FIG. 3 is a partially exploded view of the impeller assembly, drivemotor assembly, and drive shaft of the fluid mixing system;

FIG. 4 is a cross sectional side view of the first rotational assemblyshown in FIG. 3 ;

FIG. 5 is a back perspective view of the docking station shown in FIG. 1;

FIG. 6 is a perspective view of the container assembly shown in FIG. 2coupled with the drive motor assembly and yoke shown in FIG. 1 ;

FIG. 7 is a bottom perspective view of an alternative embodiment of thesupport housing shown in FIG. 1 with a yolk mounted on the exteriorsurface of the floor;

FIG. 8 is a perspective view of an alternative embodiment of an impellerassembly that can be used with the container shown in FIG. 2 ;

FIG. 9 is an exploded view of the lower rotational assembly shown inFIG. 8 ;

FIG. 10 is an enlarged perspective view of one of the impellers shown inFIG. 8 with the impeller blades in an expanded position.

FIG. 11 is a partially exploded perspective view of the impeller shownin FIG. 10 ;

FIG. 12 is a perspective view of the impeller shown in FIG. 10 with someof the blades in a collapsed position;

FIG. 13 is a perspective view of an alternative embodiment of animpeller having impeller blades with a different configuration;

FIG. 14 is a perspective view of another alternative embodiment of animpeller having different impeller blades;

FIG. 15 is a perspective view of an alternative embodiment of animpeller wherein the flexible drive line is hingedly mounted to theimpeller;

FIG. 16 is a perspective view of an alternative embodiment of animpeller wherein the drive line comprises rigid shaft sections that arehingedly mounted to opposing ends of the impeller;

FIG. 17 is a perspective view of an alternative embodiment of acontainer assembly;

FIG. 18 is a perspective view of the impeller assembly shown in FIG. 17;

FIG. 19 is a cross sectional side view of the impeller assembly shown inFIG. 18 ;

FIG. 20 is an elevational front view of an alternative embodiment of acontainer assembly containing a rigid drive shaft with an impellerhaving pivotable blades;

FIG. 21 is an elevational front view of an alternative embodiment of animpeller assembly that can be used with a rigid drive shaft;

FIG. 22 is a partial cross sectional front view of an alternativeembodiment of a fluid mixing system that includes a container assemblywith lateral support assemblies and a support housing;

FIG. 23 is a partially exploded front view of the container assemblyshown in FIG. 22 ;

FIG. 24 is a cross sectional side view of a retention assembly whichforms a portion of the lateral support assembly shown in FIG. 22 ;

FIG. 25 is a perspective view of the support housing shown in FIG. 22with support rods exploded therefrom;

FIG. 26 is a perspective view of a locking insert that is disposed onthe side of the support housing shown in FIG. 25 ;

FIG. 27A is a cross sectional side view of the retention assembly havingthe support rod partially inserted therein;

FIG. 27B is a cross sectional side view of the retention assembly havingthe support rod fully inserted and locked therein;

FIG. 28 is a cross sectional side view of a support housing having analternative embodiment of a container assembly therein when thecontainer assembly includes a rigid drive shaft;

FIG. 29 is a cross sectional side view of a support housing having analternative embodiment of a container assembly therein when the driveline is connected to both the upper end wall and the lower end wall andis supported by lateral support assemblies; and

FIG. 30 is an elevated side view of the container assembly shown in FIG.23 wherein the rotational assembly connected to the drive line has beenmoved closer to the sidewall of the support housing.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

As used in the specification and appended claims, directional terms,such as “top,” “bottom,” “left,” “right,” “up,” “down,” “upper,”“lower,” “proximal,” “distal” and the like are used herein solely toindicate relative directions and are not otherwise intended to limit thescope of the invention or claims.

The present invention relates to systems and methods for mixing fluidssuch as solutions or suspensions. The systems can be commonly used asbioreactors or fermentors for culturing cells or microorganisms. By wayof example and not by limitation, the inventive systems can be used inculturing bacteria, fungi, algae, plant cells, animal cells, protozoan,nematodes, and the like. The systems can accommodate cells andmicroorganisms that are aerobic or anaerobic and are adherent ornon-adherent. The systems can also be used in association with theformation and/or treatment of solutions and/or suspensions that are forbiological purposes, such as media, buffers, or reagents. For example,the systems can be used in the formation of media where sparging is usedto control the pH of the media through adjustment of thecarbonate/bicarbonate levels with controlled gaseous levels of carbondioxide. The systems can also be used for mixing powders or othercomponents into a liquid where sparging is not required and/or where thesolution/suspension is not for biological purposes.

Depicted in FIGS. 1-3 is one embodiment of an inventive mixing system 10incorporating features of the present invention. In general, mixingsystem 10 comprises a docking station 12, a container station 14 thatremovably docks with docking station 12, a container assembly 16 (FIG. 2) that is supported by container station 14, and a drive shaft 17 (FIG.3 ) that extends between docking station 12 and container assembly 16.Container assembly 16 houses the fluid that is mixed. The variouscomponents of mixing system 10 will now be discussed in greater detail.

As depicted in FIG. 2 , container assembly 16 comprises a container 18having a side 20 that extends from an upper end 22 to an opposing lowerend 24. Upper end 22 terminates at an upper end wall 33 while lower end24 terminates at a lower end wall 34. Container 18 also has an interiorsurface 26 that bounds a compartment 28. Compartment 28 is configured tohold a fluid. In the embodiment depicted, container 18 comprises aflexible bag that is comprised of a flexible, water impermeable materialsuch as a low-density polyethylene or other polymeric sheets or filmhaving a thickness in a range between about 0.1 mm to about 5 mm withabout 0.2 mm to about 2 mm being more common. Other thicknesses can alsobe used. The material can be comprised of a single ply material or cancomprise two or more layers which are either sealed together orseparated to form a double wall container. Where the layers are sealedtogether, the material can comprise a laminated or extruded material.The laminated material comprises two or more separately formed layersthat are subsequently secured together by an adhesive. Examples ofextruded material that can be used in the present invention include theHyQ CX3-9 and HyQ CX5-14 films available from HyClone Laboratories, Inc.out of Logan, Utah. The material can be approved for direct contact withliving cells and be capable of maintaining a solution sterile. In suchan embodiment, the material can also be sterilizable such as by ionizingradiation.

In one embodiment, container 18 can comprise a two-dimensional pillowstyle bag. In another embodiment, container 18 can be formed from acontinuous tubular extrusion of polymeric material that is cut tolength. The ends can be seamed closed or panels can be sealed over theopen ends to form a three-dimensional bag. Three-dimensional bags notonly have an annular side wall but also a two-dimensional top end walland a two-dimensional bottom end wall. Three dimensional containers cancomprise a plurality of discrete panels, typically three or more, andmore commonly four or six. Each panel is substantially identical andcomprises a portion of the side wall, top end wall, and bottom end wallof the container. Corresponding perimeter edges of each panel are seamedtogether. The seams are typically formed using methods known in the artsuch as heat energies, RF energies, sonics, or other sealing energies.

In alternative embodiments, the panels can be formed in a variety ofdifferent patterns. Further disclosure with regard to one method ofmanufacturing three-dimensional bags is disclosed in United StatesPatent Publication No. US 2002-0131654 A1, published Sep. 19, 2002,which is incorporated herein by specific reference in its entirety.

It is appreciated that container 18 can be manufactured to havevirtually any desired size, shape, and configuration. For example,container 18 can be formed having a compartment sized to 10 liters, 30liters, 100 liters, 250 liters, 500 liters, 750 liters, 1,000 liters,1,500 liters, 3,000 liters, 5,000 liters, 10,000 liters or other desiredvolumes. The size of the compartment can also be in the range betweenany two of the above volumes. Although container 18 can be any shape, inone embodiment container 18 is specifically configured to be generallycomplementary to the chamber on container station 14 in which container18 is received so that container 18 is properly supported within thechamber.

Although in the above discussed embodiment container 18 is depicted as aflexible bag, in alternative embodiments it is appreciated thatcontainer 18 can comprise any form of collapsible container orsemi-rigid container. Container 18 can also be transparent or opaque.

Continuing with FIG. 2 , formed on container 18 are a plurality of ports30 at upper end 22, a plurality of ports 31 on opposing sides of side 20at lower end 24 and a port 32 on lower end wall 34. Each of ports 30-32communicate with compartment 28. Although only a few ports 30-32 areshown, it is appreciated that container 18 can be formed with anydesired number of ports 30-32 and that ports 30-32 can be formed at anydesired location on container 18. Ports 30-32 can be the sameconfiguration or different configurations and can be used for a varietyof different purposes. For example, ports 30 can be coupled with fluidlines for delivering media, cell cultures, and/or other components intocontainer 18 and withdrawing fluid from container 18. Ports 30 can alsobe used for delivering gas to container 18, such as through a sparger,and withdrawing gas from container 18.

Ports 30-32 can also be used for coupling probes and/or sensors tocontainer 18. For example, when container 18 is used as a bioreactor orfermentor for growing cells or microorganisms, ports 30-32 can be usedfor coupling probes such as temperature probes, pH probes, dissolvedoxygen probes, and the like. Various optical sensors and other types ofsensors can also be attached to ports 30-32. Examples of ports 30-32 andhow various probes, sensors, and lines can be coupled thereto isdisclosed in United States Patent Publication No. 2006-0270036,published Nov. 30, 2006, and United States Patent Publication No.2006-0240546, published Oct. 26, 2006, which are incorporated herein byspecific reference in their entirety. Ports 30-32 can also be used forcoupling container 18 to secondary containers, to condenser systems, andto other desired fittings.

Container assembly 16 further comprises an impeller assembly 40.Impeller assembly 40 comprises a first rotational assembly 42A mountedon upper end wall 33, a second rotational assembly 42B mounted on lowerend wall 34, a flexible drive line 44 that extends between rotationalassemblies 42A and 42B, and an impeller 46 coupled to drive line 44.Drive line 44 has a longitudinal axis 48 that extends along the lengththereof and can centrally extend therethrough.

As depicted in FIG. 4 , rotational assembly 42A comprises an outercasing 50 having an outwardly projecting annular sealing flange 52 andan outwardly projecting annular mounting flange 53. A hub 54 isrotatably disposed within outer casing 50. One or more bearingassemblies 55 can be disposed between outer casing 50 and hub 54 topermit free and easy rotation of hub 54 relative to casing 50. Likewise,one or more seals 56 can be formed between outer casing 50 and hub 54 sothat during use an aseptic seal can be maintained between outer casing50 and hub 54 as hub 54 rotates relative to outer casing 50. Second end60 of hub 54 is coupled with a first end 70 of drive line 44. Thiscoupling can be by overmolding, clamp, fastener, or other conventionaltechniques. Other configurations can also be used.

Rotational assembly 42A is secured to container 18 so that second end 60of hub 54 communicates with compartment 28. Specifically, in thedepicted embodiment container 18 has an opening 74 extending throughupper end wall 33. Sealing flange 52 of outer casing 50 is sealed, suchas by welding or adhesive, around the perimeter bounding opening 74 sothat hub 54 communicates with compartment 28. Flange 52 can be welded onthe interior or exterior surface of container 18. In this configuration,outer casing 50 is fixed to container 18 but hub 54, and thus also driveline 44 and impeller 46, can freely rotate relative to outer casing 50and container 18. As a result of rotational assembly 42A sealing opening74, compartment 28 is sealed closed so that it can be used in processingsterile fluids.

Turning to FIG. 2 , rotational assembly 42B can have the sameconfiguration as rotational assembly 42A and can be mounted to lower endwall 34 of container 18 in the same manner that rotational assembly 42Ais mounted to container 18. Like elements between rotational assemblies42A and 42B are identified by like reference characters. Second end 72of drive line 44 can be mounted to hub 54 of rotational assembly 42B inthe same way that drive line 44 is connected to hub 54 of rotationalassembly 42A. As will be discussed below in greater detail, a driveshaft is used to engage and rotate hub 54 of rotational assembly 42A. Inthe above configuration, a separate drive shaft could also be used toengage and rotate hub 54 of rotational assembly 42B. In otherembodiments, hub 54 of rotational assembly 42B need not be directlyengaged and rotated by a separate drive shaft and thus opening 62 on hub54 of rotational assembly 42B can be eliminated.

Impeller 46 comprises a central hub 76 having a plurality of blades 78radially outwardly projecting therefrom. It is appreciated that avariety of different numbers and configurations of blades 78 can bemounted on hub 76. Hub 76 can be tubular so that hub 76 is slid overdrive line 44 and then secured in the desired location by crimping,welding, adhesive or using a set screw, clamp, fastener or othersecuring technique. In other embodiments, hub 76 can comprise two ormore separate members that are secured about drive line 44. In yet otherembodiments, drive line 44 can comprise two or more separate memberswhere an end of two of the members can be secured using any desiredmethod on opposing ends of hub 76. Although only one impeller 46 isshown, it is appreciated that impeller 46 can be positioned at anyposition along drive line 44 and that any number of impellers, such as2, 3, 4, or more, can be positioned along drive line 44. The impellersdisclosed herein and the alternatives discussed relative thereto areexamples of mixing elements. Mixing elements, however, also includeother structures that can be mounted on drive line 44 that can functionto mix fluid when rotated but which would not normally be considered animpeller.

Drive line 44 can be made from a variety of different flexiblematerials. By way of example and not be limitation, in one embodimentdrive line 44 can be made from a braided material such as cable, cord orrope. The braided material can be made from strands that are comprisedof metal, polymer or other materials that have desired strength andflexibility properties and can be sterilized. For example, the strandscan be made from stainless steel. In other embodiments, drive line 44can be made from a flexible tube, a single solid core line, a linkage,such as a chain or a linkage of universal joints, or other flexible orhinged members.

As depicted in FIG. 3 , impeller assembly 40 is used in conjunction withdrive shaft 17. Drive shaft 17 has a first end 84 and an opposing secondend 86. Formed at first end 84 is a frustoconical engaging portion 88that terminates at a circular plate 90. Notches 92 are formed on theperimeter edge of circular plate 90 and are used for engaging driveshaft 17 with a drive motor assembly as will be discussed below.

Formed at second end 86 of drive shaft 362 is driver portion 68. Driverportion 68 has a non-circular transverse cross section complementary toengaging portion 66 of hub 54 (FIG. 4 ) so that it can facilitatelocking engagement within engaging portion 66 of hub 54. In theembodiment depicted, driver portion 68 has a polygonal transverse crosssection. However, other non-circular shapes can also be used. It is alsoappreciated that other releasable locking mechanisms can be used toengage drive shaft 362 with hub 54. For example, a bayonet connection,threaded connection, clamp, or fastener could be used.

Returning to FIG. 1 , container station 14 comprises a support housing100 supported on a cart 102. Support housing 100 has a substantiallycylindrical sidewall 104 that extends between an upper end 106 and anopposing lower end 108. Lower end 108 has a floor 110 mounted thereto.As a result, support housing 14 has an interior surface 112 that boundsa chamber 114. An annular lip 116 is formed at upper end 106 and boundsan opening 118 to chamber 114. As discussed above, chamber 114 isconfigured to receive container assembly 16 so that container 18 issupported therein.

Although support housing 100 is shown as having a substantiallycylindrical configuration, in alternative embodiments support housing100 can have any desired shape capable of at least partially bounding acompartment. For example, sidewall 104 need not be cylindrical but canhave a variety of other transverse, cross sectional configurations suchas square, rectangular, polygonal, elliptical, or irregular.Furthermore, it is appreciated that support housing 100 can be scaled toany desired size. For example, it is envisioned that support housing 100can be sized so that chamber 114 can hold a volume of less than 50liters, more than 1,000 liters or any of the other volumes or range ofvolumes as discussed above with regard to container 18. Support housing100 is typically made of metal, such as stainless steel, but can also bemade of other materials capable of withstanding the applied loads of thepresent invention.

With continued reference to FIG. 1 , sidewall 104 of support housing 100has an enlarged access 120 at lower end 108 so as to extend throughsidewall 104. A door 122 is hingedly mounted to sidewall 104 and canselectively pivot to open and close access 120. A latch assembly 124 isused to lock door 122 in the closed position. An opening 126, which isdepicted in the form of an elongated slot, extends through door 122.Opening 126 is configured to align with ports 31 (FIG. 2 ) of containerassembly 16 when container assembly 16 is received within chamber 114 sothat ports 31 project into or can otherwise be accessed through opening126. In some embodiments, a line for carrying fluid or gas will becouple with port 31 and can extend out of chamber 114 through opening126. As previously mentioned, any number of ports 31 can be formed oncontainer 18 and thus any number of separated lines may pass out throughopening 126 or through other openings formed on support housing 100.Alternatively, different types of probes, inserts, connectors, or thelike may be coupled with ports 31 which can be accessed through opening126 or other openings.

In one embodiment of the present invention means are provided forregulating the temperature of the fluid that is contained withincontainer 18 when container 18 is disposed within support housing 100.By way of example and not by limitation, sidewall 104 can be jacketed soas to bound one or more fluid channels that encircle sidewall 104 andthat communicate with an inlet port 130 and an outlet port 132. A fluid,such as water or propylene glycol, can be pumped into the fluid channelthrough inlet port 130. The fluid then flows in a pattern aroundsidewall 104 and then exits out through outlet port 132.

By heating or otherwise controlling the temperature of the fluid that ispassed into the fluid channel, the temperature of support housing 100can be regulated which in turn regulates the temperature of the fluidwithin container 18 when container 18 is disposed within support housing100. In an alternative embodiment, electrical heating elements can bemounted on or within support housing 100. The heat from the heatingelements is transferred either directly or indirectly to container 18.Alternatively, other conventional means can also be used such as byapplying gas burners to support housing 100 or pumping the fluid out ofcontainer 18, heating the fluid and then pumping the fluid back intocontainer 18. When using container 18 as part of a bioreactor orfermentor, the means for heating can be used to heat the culture withincontainer 18 to a temperature in a range between about 30° C. to about40° C. Other temperatures can also be used.

As will be discussed below in greater detail, a yoke 140 is centrallymounted on the interior surface of floor 110 of support housing 100.Yoke 140 has a U-shaped slot 142 that is bounded by an inwardlyprojecting U-shaped catch lip 144. Yoke 140 is configured so that whencontainer assembly 16 is received within chamber 114 of support housing100, second rotational assembly 42B can be manually slid into slot 142(FIG. 3 ) so that mounting flange 53 of second rotational assembly 42Bis captured within slot 142 below catch lip 144, thereby securing secondrotational assembly 42B to yoke 140 and preventing rotational assembly42B from being raised vertically relative to yoke 140. It is appreciatedthat the function of yoke 140 is to releasably engage second rotationalassembly 42B and as such, yoke 140 can be in the form of a variety ofdifferent slots, clamps, ties, fasteners or the like. It is likewiseappreciated that second rotational assembly 42B can be attached to yoke140 by reaching in through access 120 on sidewall 104 of support housing100.

As depicted in FIG. 1 , docking station 12 comprises a stand 134, anadjustable arm assembly 136 coupled to stand 134 and a drive motorassembly 300 mounted on arm assembly 136. Drive motor assembly 300 isused in conjunction with drive shaft 17 (FIG. 3 ) and can be used formixing and/or suspending a culture, solution, suspension, or otherliquid within container 18 (FIG. 2 ). Turning to FIG. 3 , drive motorassembly 300 comprises a housing 304 having a front face 305 thatextends from a top surface 306 to an opposing bottom surface 308. Anopening 310 extends through housing 304 from top surface 306 to bottomsurface 308. A tubular motor mount 312 is rotatably secured withinopening 310 of housing 304. Upstanding from motor mount 312 is a lockingpin 316. A drive motor 314 is mounted to housing 304 and engages withmotor mount 312 so as to facilitate select rotation of motor mount 312relative to housing 304. Drive shaft 17 is configured to pass throughmotor mount 312 so that engaging portion 88 of drive shaft 17 isretained within motor mount 312 and locking pin 316 of motor mount 312is received within notch 92 of drive shaft 17. As a result, rotation ofmotor mount 312 by drive motor 314 facilitates rotation of drive shaft17. Further discussion of drive motor assembly 300 and how it engageswith drive shaft 17 and alternative designs of drive motor assembly 300are discussed in US Patent Publication No. 2011/0188928, published Aug.4, 2011, which is incorporated herein in its entirety by specificreference.

Arm assembly 136 is used to adjust the position of drive motor assembly300 and thereby also adjust the position of drive shaft 17. As depictedin FIG. 5 , arm assembly 136 comprises a first arm 320 mounted to stand134 that vertically raises and lowers, a second arm 322 mounted to thefirst arm 320 that slides horizontally back and forth, and a third arm324 mounted to second arm 322 that rotates about a horizontal axis 326.Drive motor assembly 300 is mounted to third arm 324. Accordingly, bymovements of arms 320, 322, and/or 324, drive motor assembly 300 can bepositioned in any desired location or orientation relative to supporthousing 100 and container assembly 16. For example, drive motor assembly300 can be positioned so that drive shaft 17 is centered and verticallyoriented when connected with container assembly 16. In otherembodiments, drive shaft 17 can be oriented at an angle, such as in arange between 10° to 30° from vertical when connected with containerassembly 16. Further discussion and alternative embodiments with regardto docking station 12, arm assembly 136, and container station 14 isprovided in US Patent Publication No. 2011/0310696, published Dec. 22,2011, which is incorporated herein in its entirety by specificreference.

During use, container station 14 and docking station 12 are removablycoupled together as shown in FIG. 1 . One example of how docking station12 and container assembly 16 can be coupled together is disclosed in USPatent Publication No. 2011/0310696 which was previously incorporated byreference. Other methods can also be used. Either before or aftercoupling together container station 14 and docking station 12, containerassembly 16 is positioned within chamber 114 of support housing 100 andsecond rotational assembly 42B is secured to yoke 140 as discussedabove.

In this position, arm assembly 136 is used to properly position drivemotor assembly 300 so that first rotational assembly 42A can be coupledwith drive motor assembly 300. Specifically, as depicted in FIG. 3 ,housing 304 of drive motor assembly 300 has a U-shaped receiving slot330 that is recessed on a front face 305 and bottom surface 308 so as tocommunicate with opening 310 extending through housing 304. Receivingslot 330 is bounded by an inside face 332 on which a U-shaped catch slot334 is recessed. As shown in FIG. 1 , a door 336 is hingedly mounted tohousing 304 and selectively closes the opening to receiving slot 330from front face 305. As depicted in FIG. 3 , to facilitate attachment ofrotational assembly 42A to housing 304, with door 336 rotated to an openposition, rotational assembly 42A is horizontally slid into receivingslot 330 from front face 305 of housing 304 so that mounting flange 53that is radially outwardly extending from the upper end of rotationalassembly 42A is received and secured within catch slot 334. Firstrotational assembly 42A is advanced into receiving slot 330 so thatopening 62 of rotational assembly 42A aligns with the passage extendingthrough motor mount 312. Door 336 (FIG. 1 ) is then moved to the closedposition and secured in place by a latch or other locking mechanism sothat first rotational assembly 42A is locked to drive motor assembly300.

Rotational assemblies 42A and 42B are now secured to drive motorassembly 300 and yoke 140, respectively, as shown in FIG. 6 . Armassembly 136 (FIG. 5 ) can now be used to remove any slack from or totension flexible drive line 44 by raising drive motor assembly 300 towhich rotational assembly 42A is coupled. Likewise, arm assembly 136 canbe used to adjust the orientation of drive line 44. For example, byadjusting the position of drive motor assembly 300, drive line 44 can beadjusted so as to be centered within support housing 100 and verticallyoriented or drive line 44 can be oriented at an angle, such as in arange between 10° to 30° from vertical. Other positions and orientationscan also be used.

Once first rotational assembly 42A is secured to drive motor assembly300, drive shaft 17 can be advanced down through motor mount 312 ofdrive motor assembly 300 and into opening 62 of rotational assembly 42Aso that drive shaft 17 engages with hub 54. Fluid and other componentscan be delivered into container 18. Drive motor 324 can be activated soas to rotate drive shaft 17 which in turn begins to rotate hub 54, driveline 44 and impeller 46. Where container 18 is functioning as abioreactor or fermentor, cells or microorganisms along with nutrientsand other standard components can be added to container 18. Rotation ofimpeller 46 facilitates mixing and/or suspension of the fluid andcomponents contained within container 18. Where drive line 44 is made ofa material that flexes under torsion, such as a flexible cable, cord,solid core line or the like, drive line 44 will typically be able toaxially twist along the length thereof. That is, first end 70 will beginto rotate concurrently with the rotation of hub 54 of first rotationalassembly 42A but second end 72 and hub 54 of second rotational assembly42A will not begin to rotate until drive line 44 has sufficientlytwisted along its length so that second end 72 produces a torsion forceon hub 54 of second rotational assembly 42A sufficient to overcome thefrictional resistance on hub 54. Impeller 46 also produces resistanceagainst the fluid within container 18 which results in twisting of driveline 44 during rotation. In other embodiments, such as where drive line44 is a type of linkage, axle twisting of drive line 44 may benegligible.

In one embodiment, at least a portion of drive line 44 is sufficientlyflexible so that the flexible portion of drive line 44 can be twistedunder torsion about longitudinal axis 48 of drive line 44 over an angleof at least 15°, 25°, 45°, 90°, 180°, 360°, 720° or more without plasticdeformation of drive line 44. In other embodiments, at least a portionof drive line 44 is sufficiently flexible so that the flexible portionof drive line 44 can be bent or folded relative to a linear longitudinalaxis 48 (FIG. 2 ) of drive line 44 over an angle α (FIG. 3 ) of at least15°, 25°, 45°, 90°, 135°, 180° or more without plastic deformation ofdrive line 44. Expressed in other terms, drive line 44 or the flexibleportion of drive line 44 can have a bend radius wrapped 180° withoutplastic deformation in a range between about 2 cm to about 100 cm withabout 6 cm to about 80 cm, about 10 cm to about 60 cm, or about 10 cm toabout 40 cm being more common. Other flexibilities can also be used. Itis appreciated that the entire length of drive line 44 need not beflexible. For example, a percentage of the entire length of drive shaft44, such as at least or not to exceed 30%, 40%, 50%, 60%, 70%, 80% ormore of drive shaft 44, could be flexible while the remainder is rigidor at least more rigid.

In an alternative method of use as previously mentioned, a second driveshaft could be coupled with hub 54 of second rotational assembly 42Bthough a hole formed in floor 110 of support housing 100. In thisembodiment, both ends 70 and 72 of drive line 44 could be concurrentlyrotated although there may still be some twisting of drive line 44 alonga central length or adjacent to impeller 46.

In mixing system 10, docking station 12 is used which includes armassembly 136. In this design, docking station 12 can be coupled with anynumber of different container stations 14 having a container assembly 16therein. In an alternative embodiment, however, docking station 12 canbe eliminated and arm assembly 136 can be mounted directly onto supporthousing 100. Alternative examples of arm assembles and how they can bemounted onto support housing 100 is disclosed in U.S. patent applicationSer. No. 13/659,616, filed Oct. 24, 2012 (US Patent Publication No.2013/0101982, published Apr. 25, 2013), which is incorporate herein inits entirety by specific reference.

In the above discussed embodiment depicted in FIG. 1 , yoke 140 ismounted on the interior surface of floor 110 of support housing 100 forengaging with second rotational assembly 42B (FIG. 2 ). In analternative embodiment as depicted in FIG. 7 . A yoke 140A can bemounted on the exterior surface of floor 110 of support housing 100. Ahole 148 centrally extends through floor 100 so as to communicate withchamber 114. In this embodiment, yoke 140A has an opening 149 that isbounded between a body 150 and a locking arm 152 hingedly mountedthereto. During use, with locking arm 152 in an open position, the freeend of second rotational assembly 42B (FIG. 2 ) is passed down throughhole 148 so as to be received within opening 149. Locking arm 152 isthen moved to the closed position, as shown in FIG. 7 , and secured inplace by a latch 154. In this configuration, the end of secondrotational assembly 42B is secured to yoke 140A. It is appreciated thatyokes 140 and 140A can come in a variety of other configurations andneed only be able to releasably engage the second rotational assembly.In still other embodiments, the yoke need not be secured to supporthousing 100 but can be located on a separate structure at a positionbelow support housing 100. Second rotational assembly 42B can beconfigured to pass down through hole 148 and engage with the yoke.

In one embodiment of the present invention, means are provided forholding the lower end 24 of container 18 stationary while flexible driveline 44 is rotated within compartment 28 of container 18. Examples ofthis means includes yoke 140 mounted on the interior surface of floor110, yoke 140A mounted on the exterior surface of floor 110 and yoke140A mounted on a separate structure located below floor 110.

Depicted in FIG. 8 is an alternative embodiment of an impeller assembly40A. Like elements between impeller assemblies 40 and 40A are identifiedby like reference characters. Impeller assembly 40A comprises a firstrotational assembly 160A and a second rotational assembly 160B withdrive line 44 extending therebetween. First rotational assembly 160A hassubstantially the same configuration as first rotational assembly 42Aand includes outer casing 50 having sealing flange 52 for securing tocontainer 18 and mounting flange 53. First rotational assembly 160A hasa hub 162 that rotates relative to casing 50. However, in contrast tohaving an opening 62 (FIG. 4 ) located at the end thereof, hub 162includes an outwardly projecting stem 164. Stem 164 has a non-circulartransverse cross section, such as polygonal, so that a drive shaft 17Ahaving a complementary socket 166, that replaces driver portion 68 (FIG.3 ), can securely engage with and rotate hub 162.

As depicted in FIG. 9 , second rotational assembly 160B comprises anouter casing 168 that includes a cylindrical base 170 having one or moremounting flanges 171 radially outwardly projecting from a lower endthereof and an enlarged annular sealing flange 172 radially outwardlyprojecting from the upper end thereof. Base 170 and mounting flanges 171are configured to be engaged by yoke 140A (FIG. 8 ). Sealing flange 172is configured to secure to container 18, such as by welding, in the samemanner as sealing flange 52 (FIG. 2 ). Outer casing 168 has a topsurface 174 on which a cylindrical blind pocket 176 is formed.

Second rotational assembly 160B also includes a hub 178 having a base180 to which second end 72 of drive line 44 is secured. Hub 178 alsoincludes an annular flange 182 encircling and radially outwardlyprojecting from a lower end of base 180. Flange 182 is configured sothat it can be rotatably received within blind pocket 176. Annularbearings 184A and 184B, such as roller thrust bearings, are alsoreceived within pocket 176 on opposing sides of flange 184 so that hub178 can freely rotate relative to outer casing 168. A cover plate 186encircles hub 178 and/or drive line 44 and is positioned over bearing184A. Cover plate 186 is secured in place by engaging with lockingfingers 188 that project from top surface 174 at spaced apart locationsaround pocket 176. In this configuration, cover plate 186 retains hub178 within outer casing 168. It is appreciated that because pocket 176is blind, it is not necessary to position a seal between hub 178 andouter casing 168, although a seal can be used if desired. It is alsoappreciated that the rotational assemblies can have a variety of otherconfigurations.

Returning to FIG. 8 , disposed at an upper end of drive line 44 is afoam breaker 156. Foam breaker 156 includes a hub 157 secured to driveline 44 and a bar 158 that outwardly projects from opposing sides of hub157. Foam breaker 156 rotates concurrently with drive line 44 to breakup foam that is formed at the upper end of container 18. It isappreciated that foam breaker 156 can come in a variety of differentconfigurations.

Also disposed along drive line 44 are a plurality of spaced apartimpellers 190A-D. As depicted in FIG. 10 , each impeller 190 comprises atubular hub 192 which can be advanced over drive line 44 and secured inplace such as by crimping, clamp, fastener, welding, set screw or thelike. As depicted in FIG. 11 , a flange 194 encircles and radiallyoutwardly projects from hub 192. Flange 194 has a first side face 196and an opposing second side face 198 with a plurality of openings 200Aextending therethrough adjacent to a perimeter edge of flange 194.Outwardly projecting from first side face 196 are a plurality of spacedapart stops 202 with each stop 202 being disposed adjacent to acorresponding opening 200A. Outwardly projecting from the end of eachstop 202 is a key 204.

Impeller 190 also includes a plurality of blades 206. Each blade 206comprises of an elongated arm 208 having an enlarged blade head 210located at one end and an axle 212 disposed at the opposing end. Axle212 has a first end 214 and an opposing second end 216 that project fromopposing sides of arm 208. First end 214 of axle 212 is configured to bereceived within a corresponding opening 200A so that axle 212 can rotatewithin opening 200A. An annular retainer 220 has a central passage 222through which hub 192 can be advanced. A plurality of spaced apartopenings 200B that are sized to receive second end 216 of axle 212extend between opposing sides of retainer 220. A plurality of spacedapart keyways 224 are recessed on an outer edge of retainer 220.Retainer 220 is configured to be advanced over hub 192 so that each key204 is received within a corresponding keyway 224, and second end 216 ofeach axle 212 is received within a corresponding opening 200B. Retainer220 can be secured to keys 204 such as by press fit connection,adhesive, welding, fasteners, or the like. Hub 192, flange 194 andretainer 220 combine to form an impeller body to which blades 206 areattached.

In the assembled configuration, axle 212 is free to rotate withinopenings 200A and 200B so that blades 206 are movable between acollapsed position, such as where a blade 206A is folded toward flange194 in FIG. 12 , and an extended position, such as where blade 206A isfolded away from flange 194 in FIG. 11 . In the extended position, arm208 hits against stop 202 to prevent further rotation away from thecollapsed position. Blades 206 typically radially outwardly project fromhub 102 when in the extended position but can project at angles relativeto hub 102. In most embodiments, however, an outer tip 223 of blades 206is spaced farther from hub 192 when in the extended position than whenin the collapsed position.

In alternative embodiments, it is appreciated that there are a widevariety of different ways in which blades 206 can be rotatably connectedto hub 192. For example, axles 212 could be rigidly fixed to flange 194and/or retainer 220. Arms 208 could then pivot about axles 212. Inanother embodiment, axles 212 could be hingedly secured to flange 194 soas to eliminate the need for retainer 220. In addition, both flange 194and retainer 220 could be integrally formed as a unitary member with hub192 and blades 206 could be snap fit or otherwise secured therebetween.Other alternatives also exist.

During sterilization, transport, storage, and at other times, in can bedesirable to fold up or roll up container 18 into a more compactstructure so that it is easier to handle and occupies less space. Bymaking drive line 44 out of a flexible material, this enables drive line44 to be concurrently folded up or rolled up with container 18. Use ofthe flexible drive line also eliminates the need for an elongated driveshaft which can be expensive to make and difficult to attach,particularly in low ceiling environments. Furthermore, by making blades206 movable between the collapsed and extended position, some or all ofthe blades can be moved to the collapsed position during the folding orrolling up of container 18. Collapsing of the blades enables container18 to be folded smaller, helps prevents blades 206 from puncturingcontainer 18 and can result in less stress being placed on blade 206.However, as will be discussed below in greater detail, as each impeller190 is rotated within the fluid contained within container 18, each ofblades 206 catch the fluid and automatically move to the expandedposition which is a more optimal position for mixing the fluid.

Another benefit of the inventive impeller 190 is that it is a modularsystem that can be used within a variety of different bladeconfigurations. For example, in the embodiment depicted in FIG. 10 ,each blade 206 has a blade head 210 having a generally flat rectangularconfiguration. This configuration of blade is commonly referred to as aRushton blade. Depicted in FIG. 13 is an impeller 225 with like elementsbetween impeller 190 and impeller 225 being identified by like referencecharacters. The only difference between impellers 225 and 190 is that inimpeller 225, blades 206 have been replaced with blades 226. Blades 226include arm 208 and axle 212 but in contrast to having a flatrectangular blade head 210, they have a blade head 228 having a curvedsurface. More specifically, blade head 228 has a length with an archedor substantially semi-circular transverse cross section along thelength. Again, each of blades 226 can be moved from a collapsed positionto an extended position. Depicted in FIG. 14 is still another embodimentof an impeller 230 having foldable blades 232 with a blade head 234 thatslopes relative to the longitudinal axis of hub 192.

In each of impellers 190, 225, and 230, the same impeller body can beused with blades of any desired configuration or size. Furthermore, theexchangeable blades need not be rotatable but can be designed to befixed in the extended position. Such, modular impellers provide greaterflexibility in being able to easily produce impellers having a desiredconfiguration and mixing properties while maintaining a minimum numberof stock parts.

Depicted in FIG. 15 is an alternative embodiment of an impeller 238 thatis hingedly mounted to drive line 44. Like elements between impellers190 and 238 are identified by like reference characters. Impeller 238 issubstantially identical to impeller 190 except that in contrast to hub192 (FIG. 10 ) which is tubular and received over drive line 44,impeller 238 includes an elongated hub 240 having a first end 242 with aU-shaped connecter 244A formed thereat and an opposing second end 246with a U-shape connector 244B formed thereat. Each of connectors 244Aand B bound a slot 248 and have an opening 250 transversely extendingtherethrough. Flexible line 44 is comprised of line portion 252A havingconnector 254A mounted on the end thereof and line portion 252B having aconnector 254B mounted on the end thereof. Each of connecters 254A and Balso have an opening 256 transversely extending therethrough. Duringassembly, connectors 254A and B are received within slots 248 ofU-shaped connectors 244A and B, respectively, so that openings 250 and256 are aligned. Hinge pins 258 are then received within alignedopenings 250 and 256 and secured in place so that connectors 254A and Bcan freely pivot relative to impeller 238. Hinge pins 258 can beattached to connectors 244A and B by being press fit, welded, threadedor using other conventional techniques. In alternative embodiments, itis appreciated that a variety of different unions, hinges, swivels, andthe like can be used to hingedly connect line portions 252A and B toopposing ends of hub 240. Furthermore, although impeller 238 is shownhaving pivotably mounted blades 206, in an alternative embodimentimpeller 238 can be formed with fixed blades.

FIG. 16 again depicts impeller 238. However, in contrast to beinghingedly coupled to flexible drive line 44, impeller 238 in FIG. 16 ishingedly coupled to line portions 262A and B of a rigid drive line 264.That is, line portions 262A and B can have openings 256 extendingtherethrough and can be made of shafts, rods or tubes or the like thatare comprised of or consist of metal, plastics, composites, or the likethat are substantially rigid or have limited flexibility. For example,line portions 262A and B can have a bend radius wrapped 90° that must begreater than 8 meters, 10 meters or 12 meters to prevent plasticdeformation.

Depicted in FIG. 17 is a perspective view of an alternative embodimentof a container assembly 16B that includes an alternative embodiment of aflexible drive line. Container assembly 16B can be operated withinsupport housing 100 (FIG. 1 ) in substantially the same manner as theother container assemblies discussed herein. Specifically, containerassembly 16B comprises container 18 having an impeller assembly 40Bcoupled thereto. Impeller assembly 40B comprises a first rotationalassembly 270 mounted to upper end wall 33 of container 18 and a secondrotational assembly 242 mounted to lower end wall 34 of container 18. Asdepicted in FIGS. 18 and 19 , upper rotational assembly 270 comprisesouter casing 50 and hub 162 as previously discussed. Various bearingassemblies 274 can be positioned between outer casing 50 and hub 162 tofacilitate ease of rotation of hub 162. One or more seals 276 can alsobe positioned between outer casing 50 and hub 162 to form a liquid-tightseal therebetween. An adapter 278 is coupled with hub 162 and has a stem280 that projects away from hub 162. In an alternative embodiment, stem280 can be integrally formed as a unitary structure with hub 162.

Second rotational assembly 272 includes outer casing 168, bearings 184Aand B and cover plate 186 as previously discussed. Second rotationalassembly 272 also includes a hub 284 having an upwardly extending stem286 that passes through cover plate 186 and an outwardly projectingflange 288 that is positioned between bearings 184A and B. Locatedbetween rotational assemblies 270 and 272 is an impeller 290. Impeller290 comprises a tubular hub 291 having a first end 292 and an opposingsecond end 293. Flange 194 encircles and radially outwardly projectsfrom hub 291. Blades 206 hingedly mounted between flange 194 andretainer 220 as previously discussed. In an alternative embodiment,fixed blades can be secured to hub 291 or flange 194.

Drive line assembly 40B also includes a flexible drive line 44B thatincludes a drive line portion 294A and a drive line portion 294B. Eachof drive line portions 294 comprise a flexible tube that can be made ofa resiliently flexible plastic or other material. In the depictedembodiments, although not required, the tubes are corrugated so as toincrease flexibility. Drive line portions 294 can have the sameflexibility as drive line 44 as previously discussed. Drive line portion294A has a first end 295 that is received over and coupled to stem 280and an opposing second end 296 that is received within and secured tofirst end 292 of hub 291. Similarly drive line portion 294B has a firstend 297 received over and secured to stem 286 and an opposing second end298 received within and secured to second end 293 of hub 291. In thisconfiguration, rotation of hub 162 of first rotational assembly 270facilitates rotation of drive line portions 294A and B, impeller 290,and hub 284 of second rotational assembly 272.

Although the above discussed embodiments primarily disclose the use ofimpellers having pivotable blades with flexible drive lines, it isappreciated that the inventive impellers of the present invention canalso be used with rigid drive shafts. For example, depicted in FIG. 20is a container assembly 16C that includes container 18. A dynamic seal350 is mounted on upper end wall 33. A rigid drive shaft 352 passesthrough dynamic seal 350 and has a first end 354 disposed outside ofcontainer 18 and an opposing second end 356 disposed within container18. Dynamic seal 350 enables drive shaft 352 to freely rotate relativeto container 18 while forming an aseptic seal between container 18 anddrive shaft 352. A driver portion 358, which can have a polygonal orother noncircular transverse cross section or some other engagingsurface, can be formed at first end 354 so that a drive motor can engagewith and rotate drive shaft 352.

Mounted on second end 356 of drive shaft 352 is impeller 190 aspreviously discussed herein. Rotation of drive shaft 356 causes blades206 to move to the expanded position and mix the fluid within container18. Impeller 190 can be replaced with the other impellers discussedherein having pivotable blades and can incorporate other alternativeconfigurations as discussed herein. Again, as a result of pivotableblades 206, container 18 can be more fully collapsed around impeller 190while minimizing risk of damage to container 18 and to blades 206.

Depicted in FIG. 21 is another alternative embodiment of mixing systemthat incorporates an impeller with pivotable or foldable blades. Themixing system includes an impeller assembly 40C that comprises anelongated tubular connector 542 having a rotational assembly 548 mountedat one end and an impeller 564 or other mixing element mounted on theopposing end. More specifically, tubular connector 542 has a first end544 and an opposing second end 546 with a passage 549 that extendstherebetween. In one embodiment, tubular connector 542 comprises aflexible tube, such as a polymeric tube, having the same flexibility asdiscussed above with regard to drive line 44. As such, tubular connector542 can comprise a flexible drive line as claimed herein. In otherembodiments, tubular connector 542 can comprise a rigid tube or othertubular structure.

Rotational assembly 548 is mounted to first end 544 of tubular connector542. Rotational assembly 548 comprises outer casing 50 having anoutwardly projecting annular sealing flange 52 and an outwardlyprojecting mounting flange 53 as previously discussed. A tubular hub 454is rotatably disposed within outer casing 50. One or more bearingassemblies, as previously discussed, can be disposed between outercasing 50 and hub 554 to permit free and easy rotation of hub 554relative to casing 50. Likewise, one or more seals, as previouslydiscussed, can be formed between outer casing 50 and hub 554 so thatduring use an aseptic seal can be maintained between outer casing 50 andhub 554.

Hub 554 has an interior surface 556 that bounds an opening 558 extendingtherethrough. Interior surface 556 includes an engaging portion having apolygonal or other non-circular transverse cross section so that driverportion 68 of drive shaft 362, as also shown in FIG. 21 , passingthrough opening 558 can engage the engaging portion and facilitaterotation of hub 554 by rotation of drive shaft 362. Hub 554 can alsocomprise a tubular stem 560 projecting away from outer casing 50. Hub554 can couple with first end 544 of tubular connector 542 by stem 560being received within first end 544. A pull tie, clamp, crimp or otherfastener can then be used to further secure stem 560 to tubular connect542 so that a liquid tight seal is formed therebetween. Otherconventional connecting techniques can also be used.

Impeller 564 comprises a central hub 566 having blades 206 pivotablycoupled thereto through the use of flange 194 and retainer 220 aspreviously discussed with regard to FIG. 11 . Alternative embodiments asdiscussed herein with regard to other impellers having pivotable bladescan also be incorporated into impeller 564. Hub 566 has a first end 570with a blind socket 572 formed thereat. Socket 572 typically has anoncircular transverse cross section, such as polygonal, so that it canengage a driver portion 378 of drive shaft 362. Accordingly, when driverportion 378 is received within socket 572, driver portion 378 engageswith impeller 564 such that rotation of drive shaft 362 facilitiesrotation of impeller 564.

Impeller 564 can be attached to connector 542 by inserting first end 570of hub 566 within connector 542 at second end 546. A pull tie, clamp,crimp, or other type of fastener can then be cinched around second end546 of connector 542 so as to form a liquid tight sealed engagementbetween impeller 564 and connector 542.

Rotational assembly 548 is secured to container 18 in substantially thesame manner that rotational assembly 42 was secured to container 18, aspreviously discussed with regard to FIG. 2 , so that tubular connector542 and impeller 564 extend into or are disposed within compartment 28of container 18.

In general drive shaft 362 comprises a head section 364 and a shaftsection 366 that can be coupled together by threaded connection or othertechniques. Head section 364 has substantially the same configuration asdrive shaft 17 discussed with regard to FIG. 3 and thus like featureshead section 364 and drive shaft 17 will be identified by like referencecharacters. Alternatively, drive shaft 362 can be formed as a singlepiece member or from a plurality of attachable sections. Drive shaft 362has a first end 368 and an opposing second end 370. Formed at first end368 is a frustoconical engaging portion 88 as previously discussed withregard to FIG. 3 . Formed at second end 370 of drive shaft 362 is driverportion 378. Driver portion 378 has a non-circular transverse crosssection so that it can facilitate locking engagement within hub 466 ofimpeller 464. In the embodiment depicted, driver portion 378 has apolygonal transverse cross section. However, other non-circular shapescan also be used. Driver portion 68 is also formed along drive shaft 362toward first end 368. Driver portion 68 also has a non-circulartransverse cross section and is positioned so that it can facilitatelocking engagement within the engaging portion of rotational assembly448.

During use, container 18 having impeller assembly 40C coupled thereto isreceived within support housing 100 (FIG. 1 ) and rotational assembly issecured to drive motor assembly 300 as previously discussed with regardto FIG. 3 . Drive shaft 362 is advanced down through motor mount 312,hub 454 of rotational assembly 548, tubular connecter 542 and into hub566 of impeller 564. As a result of the interlocking engagement ofdriver portions 378 and 68 with hubs 566 and 554, respectively, rotationof drive shaft 362 by drive motor assembly 300 facilitates rotation ofhub 554, tubular connecter 542 and impeller 564 relative to outer casing50 of rotational assembly 548 and container 18. The rotation of impeller564 causes blades 206 to move to the expanded position and mix the fluidwithin container 18.

It is appreciated that impeller assembly 40C, drive shaft 362 and thediscrete components thereof can have a variety of differentconfiguration and can be made of a variety of different materials.Alternative embodiments of and further disclosure with respect toimpeller assembly 40C, drive shaft 362, and the components thereof aredisclosed in U.S. Pat. No. 7,384,783, issued Jun. 10, 2008, and USPatent Publication No. 2011/0188928, published Aug. 4, 2011, which areincorporated herein in their entirety by specific reference.

In the prior discussed embodiments incorporating the flexible driveline, the flexible drive line is supported by being secured to both theupper end wall and lower end wall of the container. In an alternativeembodiment, the flexible drive line can be supported and stabilized bybeing secured to the upper end wall of the container and at one or morelocations along the length of the flexible drive line. For example,depicted in FIG. 22 is an alternative embodiment of a fluid mixingsystem 10A incorporating features of the present invention. Fluid mixingsystem 10A comprises a container assembly 16D at least partiallydisposed within the compartment of a support housing 100A. Like elementsbetween container assembly 16 and 16A and between support housing 100and 100A are identified by like reference characters. Furthermore,disclosure and alternative embodiments as previously discussed withregard to container 16 and support housing 100 are also applicable tocorresponding elements of container assembly 16A and support housing100A.

As depicted in FIG. 23 , container assembly 16A comprises container 18having flexible drive line 44 disposed therein. First end 70 of flexibledrive line 44 is secured to upper end wall 33 of container 18 byrotational assembly 42A. Mounted on flexible drive line 44 as spacedapart locations are mixing elements 400A-C. Each of mixing element400A-C can comprise a fixed blade impeller, such as previously discussedimpeller 46, a foldable impeller, such as previously discussed impellers190, 225, 230, 238, or other types of mixing elements. In alternativeembodiments, container assembly 16A can comprise one, two, or four ormore mixing elements 400. In contrast to container assembly 16 wheresecond end 72 of drive line 44 is secured to lower end wall 34,container assembly 16A has second end 72 of drive line 44 suspendedabove lower end wall 34.

To stabilize drive line 44 within compartment 28 of container 18,container assembly 16A comprises lateral support assemblies 402A-Ccoupled with flexible drive line 44 at space apart locations along thelength thereof. Each lateral support assembly 402A-C comprises aretention assembly 404 having a first end 405 secured to side 20 ofcontainer 18 and an opposing second end 407 secured to flexible driveline 44. Lateral support assembly 402 also includes a support rod 406that is selectively received and secured within corresponding retentionassembly 404. Each retention assembly 404 comprises a port fitting 410at first end 405 that is coupled with side 20 of container 18, areceiver 408 at second end 407 that is mounted to flexible drive line44, and a flexible tube 412 that extends between port fitting 410 andreceiver 408.

As depicted in FIG. 24 , receiver 408 comprises an inner housing 414that is securely fixed to flexible drive line 44 such as by crimping,adhesive, clamps, fasteners, or the like. Receiver 408 also includes anouter housing 416 that encircles inner housing 414. A bearing 418, suchas a ball thrust bearing, roller thrust bearing, or other type ofbearing, is disposed between inner housing 414 and outer housing 416.Bearing 418 enables inner housing 414 and drive line 44 to rotateconcurrently relative to outer housing 416. Outer housing 416 includes abody 420 having a tubular stem 422 outwardly projecting therefrom. Stem422 can be integrally formed with or secured to body 420. An annularbarb 423 can encircle and outwardly project on the end of stem 422 forengaging with flexible tube 412. Stem 422 has an interior surface 424that bounds an opening 426 that can extend into body 420. Formed oninterior surface 424 of stem 422 and/or body 420 is an engaging thread428.

As also depicted in FIG. 24 , port fitting 410 comprises a tubular stem430 having a first end 432 and an opposing second end 434. An annularbarb 436 can encircle and outwardly extending from second end 434 forengaging with flexible tube 412. Radially outwardly projecting fromfirst end 432 is a retention flange 438. As will be discussed below ingreater detail, retention flange 438 is used to secure port fitting 410to rigid support housing 100. Retention flange 438 need not encirclestem 430 and can have a variety of different configurations. Encirclingand radially outwardly projecting from stem 430 at a location betweenopposing ends 432 and 434 is a mounting flange 440. Mounting flange 440is welded or otherwise secured to side 20 of container 18 so as to forma liquid tight seal therewith. As a result, first end 432 of portfitting 410 disposed outside of container 18 while second end 434 isdisposed within container 18. Stem 430 has an interior surface 442 thatbounds a passageway 444 extending therethrough.

Flexible tube 412 can comprise any type of flexible tube, tubing, hose,pipe or the like and is typically comprised of an elastomeric polymer.By making tube 412 flexible, tube 412 can be folded or rolled whencollapsing container 18 for shipping, storage, disposal or the like. Inan alternative embodiment it is appreciated that tube 412 need not beflexible but can be rigid or semi-rigid. Tube 412 has an interiorsurface 446 that bounds a passageway 448 that longitudinally extendsthrough tube 412 from a first end 450 to an opposing second end 452.First end 450 of tube 412 is advanced over stem 430 of port fitting 410so as to form a liquid tight seal therewith while second end 452 of tube412 is received over stem 422 of receiver 408 so as to form a liquidtight seal therewith. A fastener 454 such as a pull tie, crimp, clamp,or similar structure can be secured around first end 450 and second end452 so as to secure the engagement between tube 412 and stems 422 and430.

During use, as depicted in FIG. 22 , container assembly 16D is receivedwithin chamber 114 of support housing 100A. Support housing 100A issubstantially identical is support housing 100 as previously discussedwith regard to FIG. 1 and like elements are identified by like referencecharacters. Support housing 100A is distinguished from support housing100 in that it does not include yoke 140 located on floor 110 (FIG. 1 ).Rather, support housing 100A includes a plurality of locking fittings460A-C mounted at spaced apart locations on sidewall 104. As depicted inFIGS. 25 and 26 , each locking fitting 460 comprises a base 462 having afirst end 464 and an opposing second end 466. A passageway 468 centrallypasses through base 462 between opposing ends 464 and 466. A flange 470can encircle and radially outwardly project from base 462 at a locationbetween opposing ends 464 and 466. During the manufacture of supporthousing 100A, vertically spaced apart holes 475 (FIG. 22 ) can be formedthrough sidewall 104 so as to extend to chamber 114. Second end 466 ofeach locking fitting 460 is received within a corresponding hole 475 sothat flange 470 hits against the exterior surface of sidewall 104.Welding or other fastening techniques can then be used to secure eachlocking fitting 460 to support housing 100A within the correspondinghole 475.

Formed on the end face of base 462 at second end 466 is a catch 472.Catch 472 is disposed adjacent to interior surface 112 of supporthousing 100A and has a U-shaped body 474 with a U-shaped opening 476passing therethrough. U-shaped opening 476 is aligned with passageway468 passing through base 462. Body 474 has an interior surface 478 thatincludes an undercut U-shaped channel 480 and a U-shaped catch lip 482that radially inwardly projects adjacent to channel 480. Catch 472 isconfigured so that retention flange 438 on port fitting 410 can beslidably received and captured within channel 480 so that passageway 468of locking fitting 460 is aligned with passageway 444 of a correspondingport fitting 410. It is appreciated that retention flange 438 and/orchannel 480 can be tapered so that a releasable friction fit is formedtherebetween. It is also appreciated that there are a variety ofdifferent fastening techniques that can be used to releasably secureport fitting 410 to locking fitting 460.

Locking fitting 460 also includes a locking slot 486 formed on first end464 of base 462 and which is located outside of support housing 100A.Locking slot 486 includes a first leg 488 that passes through base 462to passageway 468 and runs parallel to passageway 468. Locking slot 486also includes a second leg 490 that extends normal to first leg 488 atthe end thereof so as to extend around a portion of the perimeter ofbase 462. Second leg 490 also extends to passageway 468.

Returning to FIG. 25 , each support rod 406 comprises a linear shaft 500that extends between a first end 502 and an opposing second end 504. Alocking thread 506 is formed on second end 504. A locking arm 508radially outwardly projects from shaft 500 as first end 502. Locking arm508 is sized to be received within locking slot 486. Support rod 406 istypically comprised of metal but other rigid or semi-rigid materials canalso be used.

During use, as previously discussed and depicted in FIG. 22 , containerassembly 16D is received within chamber 114 of support housing 100A.Once inserted, each port fitting 410 is secured to a correspondinglocking fitting 460 as previously discussed and depicted in FIG. 27A. Inthis assembled configuration, second end 504 of each support rod 406 isadvanced through passageway 468 of locking fitting 460 throughpassageway 444 of port fitting 410 and into passageway 448 of tube 412.Each support rod 406 is continued to be advanced until locking thread506 reach engaging thread 428 on retention assembly 404. Concurrently,locking arm 508 is received within first leg 488 (FIG. 26 ) of lockingslot 486. In this position, locking arm 508 can be rotated downwardthrough second leg 490 of locking slot 406 so as to lock support rod 406to locking fitting 460. As locking arm 508 is rotated, shaft 500 withlocking threads 506 thereon are rotated. As locking threads 506 arerotated they threadedly engage with engaging threads 428 on receiver408, thereby securing support rod 406 to receiver 408. As a result,opposing ends of support rod 406 are secured to locking fitting 460 andreceiver 408 which creates a lateral rigid support for flexible driveline 44. It is appreciated that a variety of other connections can beused for securing one or both of opposing ends of support rod 404 suchas a bayonet connection, luer-lock connection, clamp, separate fastener,or the like.

The lateral rigid support of flexible drive line 44 achieves a number ofbenefits. For example, where mixing element 400 is an impeller, therotation of the impeller causes the impeller to tend to migratelaterally. Lateral movement of drive line 44 and mixing elements 400 cancause damage to container 18 and can produce irregular mixing withincontainer 14. Irregular mixing can be especially problematic where themixing system is being used as a bioreactor or fermetor used for growingcells or microorganisms. In those cases, irregular mixing can applyunwanted shear forces on the cells or microorganisms or can result inirregular feeding or gas transfer to the cells or microorganisms. Use ofthe lateral support assemblies prevents unwanted lateral movement ofdrive line 44 and mixing elements 400 within container 18 and helpsmaintain uniform mixing. Although in the depicted embodiment threeseparate lateral support assemblies 402 are shown, in alternativeembodiments, container assembly 16D can be formed with only one or twolateral support assemblies. Alternatively, four or more lateral supportassemblies can also be used based on the size or other operationalconditions for container assembly 16D.

Furthermore, as a result of the lateral support to drive line 44, secondend 72 of drive line 44 need not be connected to lower end wall 34 ofcontainer 18. In some cases this is beneficial because it permits a moreconvenient folding of container 18. That is, in some designs forcontainer 18, the most compact folding of container 18 requires that thecenter of opposing end walls 33 and 34 be pulled away from each other.Where drive line 44 is secured to the opposing end walls 33 and 34, theend walls cannot be pulled away from each other and thus container 18cannot be folded in the most compact manner.

In addition, where the opposing ends of drive line 44 are connected tothe top and bottom of container 18, as in FIG. 2 , drive line 44 istensioned to help prevent lateral walking of the impeller. As previouslydiscussed, to facilitate the tension of drive line 44, the second end ofcontainer 18 is secured to the floor or relative to the floor of thesupport housing. In contrast, by using the lateral support assemblies,drive line 44 does not need to be tensioned and it is not necessary tosecure the second end of container 18 to the floor of the supporthousing.

Depicted in FIG. 28 is a container assembly 16E disposed within supporthousing 100A. Container assembly 16E includes lateral support assemblies402A-C. However, in contrast to being connected to flexible drive line44, container assembly 16E includes a rigid drive shaft 516 such asdrive shaft 352 as depicted in FIG. 20 . Lateral support assemblies 402facilitate the lateral support of drive shaft 516 along the lengththereof. Again, any number of lateral support assemblies 402 can be usedand any number of mixing elements 400 can be mounted thereon. Otheralternative embodiments as previously discussed with regard to likeelements of container assembly 16D are also applicable containerassembly 16D.

In another alternative embodiment, a container assembly can be formedthat includes impeller assembly 40C as depicted and previously discussedwith regard to FIG. 21 . One or more lateral support assemblies 402 canextend between the side of container 18 and tubular connector 442. Thecontainer assembly can be housed within support housing 100A.

Depicted in FIG. 29 is another alternative embodiment of a containerassembly 16F disposed within support housing 100A. Container assembly16F is used where greater stability of drive line 44 is required, suchas for long containers 18. Container assembly 16F comprises container 18housing drive line 44 on which one or more mixing elements 400 aredisposed. First end 70 of drive line 44 is secured to upper end wall 33by first rotational assembly 42A and second end 72 of drive line 44 issecured to lower end wall 34 by second rotational assembly 42B in thesame manner as previously discussed with regard to container assembly 16depicted in FIGS. 2 and 3 . In turn, second rotational assembly 42B canbe secured to floor 110 of support housing 100A using one of the yokespreviously discussed or can be otherwise secured in place. Containerassembly 16F also includes one or more lateral support assemblies 402extending between side 20 of container 18 and flexible drive line 44 aspreviously discussed with regard to container assembly 16D depicted inFIGS. 22-24 . Thus, in this embodiment flexible drive line 44 issupported both at opposing ends and at one or more locations along itslength. Use and alternative embodiments as discussed with the othercontainer assemblies are also applicable to container assembly 16F.

Finally, depicted in FIG. 30 is another alternative embodiment of acontainer assembly 16G disposed within support housing 100A. Containerassembly 16G is substantially the same as container assembly 16D andthus the prior disclosure, alternative embodiments and referencecharacters for container assembly 16D are also applicable to containerassembly 16E. Container 18 has a central longitudinal axis 520 thatextends between upper end wall 33 and lower end wall 34. In containerassembly 16D, rotational assembly 42A is mounted on upper end wall 33 inalignment with central longitudinal axis 520 and drive line 44 extendsalong central longitudinal axis 520. In contrast, container assembly 16Ghas rotational assembly 42A disposed on upper end wall 33 at a locationspaced apart from central longitudinal axis 520 and, more specifically,adjacent to sidewall 104 of support housing 100A. However, lateralsupport assemblies 402 hold the portion of drive line 44 on which mixingelements 400 are disposed, along central longitudinal axis 520.

Container assembly 16G has the advantage that mixing elements 400 arestill centrally disposed within container 18 so that the fluid withincontainer 18 can have uniform mixing but the central area of upper endwall 33 is now openly exposed. As such, ports, fitting, probes, sampletubes and the like can now be centrally mounted on upper end wall 33,which is often considered a valuable location. Furthermore, placingrotational assembly 42A closer to sidewall 104 of support housing 100Acan make it easier to connect rotational assembly 42A to drive motorassembly 300 (FIG. 1 ). Thus, because of the flexible nature of driveline 44 and the rigid lateral support produced by lateral supportassemblies 402, rotational assembly 42A can be located at any positionon upper end wall 33 and even at the upper end of side 20 of container18.

The present invention may be embodied in other specific forms withoutdeparting from its spirit or essential characteristics. The describedembodiments are to be considered in all respects only as illustrativeand not restrictive. The scope of the invention is, therefore, indicatedby the appended claims rather than by the foregoing description. Allchanges which come within the meaning and range of equivalency of theclaims are to be embraced within their scope.

What is claimed is:
 1. A method of mixing a fluid, the methodcomprising: at least partially unfolding a collapsible bag bounding acompartment, the collapsible bag containing in the compartment at leasta portion of an elongated drive line or drive shaft and an impellersecured to the drive line or drive shaft, the impeller including aplurality of impeller blades that are pivotable relative to the driveline or drive shaft, at least one of the plurality of impeller bladesbeing in a collapsed position; delivering a fluid into the compartmentof the collapsible bag; and rotating the drive line or drive shaft so asto rotate the impeller within the compartment and mix the fluid therein,the at least one of the plurality of impeller blades pivoting from thecollapsed position to an expanded position as the impeller is rotatedwithin the compartment.
 2. The method as recited in claim 1, wherein theimpeller comprises a hub secured to the drive line or drive shaft, eachof the plurality of impeller blades being pivotably coupled to the hub.3. The method as recited in claim 1, wherein the impeller comprises ahub secured to the drive line or drive shaft and a flange radiallyoutwardly projecting from the hub, the hub having a central longitudinalaxis extending therethrough, each of the plurality of impeller bladesbeing pivotably coupled to the flange.
 4. The method as recited in claim3, further comprising a retainer at least partially encircling the huband being secured to the flange, each of the plurality of impellerblades being pivotably secured between the flange and the retainer. 5.The method as recited in claim 3, wherein the flange and the retainerboth completely encircle the hub.
 6. The method as recited in claim 3,wherein each of the plurality of impeller blades comprise: an elongatedarm longitudinally extending between a first end and an opposing secondend, the first end being pivotably coupled to the flange so that theelongated arm pivots about a rotational axis, the rotational axis beingdisposed parallel to the central longitudinal axis of the hub; and anenlarged blade head disposed at the second end of the elongated arm. 7.The method as recited in claim 1, wherein each of the plurality ofimpeller blades are pivotable between a collapsed position and anexpanded position, each of the impeller blades having a terminal tipthat is closer to the drive line or drive shaft when the impeller bladesare in the collapsed position than when in the expanded position.
 8. Themethod as recited in claim 7, wherein each of the plurality of bladesare mechanically stopped when moved to the collapsed position and theexpanded position
 9. The method as recited in claim 1, wherein thecollapsible bag is comprised of one or more sheets of polymeric film.10. The method as recited in claim 1, wherein the elongated drive lineor drive shaft comprises the drive line, the drive line being at leastpartially disposed within the compartment of the collapsible bag andhaving the impeller secured thereto, wherein at least 30% of the driveline within the compartment is sufficiently flexible that it can betwisted under torsion over an angle of at least 45° without plasticdeformation.
 11. The method as recited in claim 10, further comprisingcoupling a drive shaft to the drive line such that rotation of the driveshaft outside of the collapsible bag facilitates rotation of the driveline within the collapsible bag.
 12. The method as recited in claim 10,wherein the drive line has a length extending between a first endrotatable connected to a first end of the collapsible bag and a secondend rotatably connected to a second end of the collapsible bag.
 13. Themethod as recited in claim 10, wherein the drive line is comprised of aflexible cable, cord, or tube.
 14. The method as recited in claim 10,wherein the drive line comprises a flexible tube and the method furthercomprises removably inserting a drive shaft within the flexible tube,the drive shaft engaging with the flexible tube or the impeller suchthat rotation of the drive shaft causes rotation of the impeller. 15.The method as recited in claim 1, further comprising: the elongateddrive line or drive shaft comprising the drive shaft, the drive shaftbeing at least partially disposed within the compartment of thecollapsible bag; and a dynamic seal sealing the drive shaft to thecollapsible bag.
 16. The method as recited in claim 1, furthercomprising positioning the collapsible bag within a chamber of a supporthousing, the support housing having a floor and an sidewall upstandingfrom the floor
 17. The method as recited in claim 1, further comprisingsecuring the collapsible bag to the floor of the support housing.